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Management of encephalitis

management of encephalitis

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Management of encephalitis

  2. 2. Grading System for ranking recommendations in clinical guidelines Strength of recommendation Definition A Good evidence to support a recommendation for use B Moderate evidence to support a recommendation for use C Poor evidence to support a recommendation Quality of evidence Definition I Evidence from 1 properly randomized, controlled trial II Evidence from 1 well-designed clinical trial, without randomization; from cohort or case-controlled analytical studies; from multiple time-series; or from dramatic results from uncontrolled experiments III Evidence from opinions of respected authorities, based on clinical experience, descriptive studies, or reports of expert committees
  3. 3. Etiology  1. Epidemiologic clues and assessment of risk factors to identify potential etiologic agents should be sought in all patients with encephalitis (A-III).  2. Clinical clues (general and specific neurologic findings) may be helpful in suggesting certain causative agents in patients with encephalitis (B-III).  3. In patients with encephalitis and a history of recent infectious illness or vaccination, the diagnosis of ADEM should be considered (B-III).
  4. 4. Possible etiologic agents of encephalitis based on epidemiology and risk factors Epidemiology or risk factor Possible infectious agent(s) Agammaglobulinemia Enteroviruses, Mycoplasma pneumoniae AGE Neonates Herpes simplex virus type 2, cytomegalovirus, rubella virus, Listeria monocytogenes, Treponema pallidum, Toxoplasma gondii Infants and children Eastern equine encephalitis virus, Japanese encephalitis virus, Murray Valley encephalitis virus, influenza virus, La Crosse virus Elderly persons Eastern equine encephalitis virus, St. Louis encephalitis virus, West Nile virus, sporadic CJD, L. monocytogenes
  5. 5. ANIMAL CONTACTS Bats Rabies virus, Nipah virus Birds West Nile virus, Eastern equine encephalitis virus, Western equine encephalitis virus, Venezuelan equine encephalitis virus, St. Louis encephalitis virus, Murray Valley encephalitis virus, Japanese encephalitis virus, Cryptococcus neoformans (bird droppings) Cats Rabies virus, Coxiella burnetii, Bartonella henselae, T. gondii Dogs Rabies virus Horses Eastern equine encephalitis virus, Western equine encephalitis virus,Venezuelan equine encephalitis virus, Hendra virus Raccoons Rabies virus, Baylisascaris procyonis Rodents Eastern equine encephalitis virus (South America), Venezuelan equine encephalitis virus, tickborne encephalitis virus, Powassan virus (woodchucks), La Crosse virus (chipmunks and squirrels), Bartonella quintanab
  6. 6. Sheep and goats C. burnetii Swine Japanese encephalitis virus, Nipah virus Immunocompromis ed persons Varicella zoster virus, cytomegalovirus, human herpesvirus 6, West Nile virus, HIV, JC virus, L. monocytogenes, Mycobacterium tuberculosis, C. neoformans, Coccidioides species, Histoplasma capsulatum, T. gondii Ingestion items Raw meat T. gondii Unpasteurized milk Tickborne encephalitis virus, L. monocytogenes, C. burnetii Insect contact Mosquitoes Eastern equine encephalitis virus, Western equine encephalitis virus, Venezuelan equine encephalitis virus, St. Louis encephalitis virus, Murray Valley encephalitis virus, Japanese encephalitis virus, West Nile virus, La Crosse virus, Plasmodium falciparum Ticks Tickborne encephalitis virus, Powassan virus, Rickettsia rickettsii, Ehrlichia chaffeensis, Anaplasma phagocytophilum, C. burnetii (rare), B. burgdorfer
  7. 7. Sandflies Bartonella bacilliformis Tsetse flies Trypanosoma brucei gambiense, Trypanosoma brucei rhodesiense Occupation Laboratory workers West Nile virus, HIV, C. burnetii, Coccidioides species Physicians and health care workers Varicella zoster virus, HIV, influenza virus, measles virus, M. tuberculosis Veterinarians Rabies virus, Bartonella species, C. burnetii Recent vaccination Acute disseminated encephalomyelitis Person-to-person transmission Herpes simplex virus (neonatal), varicella zoster virus, Venezuelan equine encephalitis virus (rare), poliovirus, nonpolio enteroviruses, measles virus, Nipah virus, mumps virus, rubella virus, Epstein-Barr virus, human herpesvirus 6, B virus, West Nile virus (transfusion, transplantation, breast feeding), HIV, rabies virus (transplantation), influenza virus, M. pneumoniae, M. tuberculosis, T. pallidum
  8. 8. Recreational activities Camping/hunting All agents transmitted by mosquitoes and ticks Sexual contact HIV, T. pallidum Swimming Enteroviruses, Naegleria fowleri Season Late summer/early fall All agents transmitted by mosquitoes and ticks ,enteroviruses Winter Influenza virus Travel Africa Rabies virus, West Nile virus, P. falciparum, T. brucei gambiense, T. brucei rhodesiense Australia Murray Valley encephalitis virus, Japanese encephalitis virus, Hendra virus Europe West Nile virus, tickborne encephalitis virus, A. phagocytophilum, B. burgdorferi India, Nepal Rabies virus, Japanese encephalitis virus, P. falciparum
  9. 9. Central America Rabies virus, Eastern equine encephalitis virus, Western equine encephalitisvirus, Venezuelan equine encephalitis virus, St. Louis encephalitis virus, R. rickettsii, P. falciparum, Taenia solium South America Rabies virus, Eastern equine encephalitis virus, Western equine encephalitis virus, Venezuelan equine encephalitis virus, St. Louis encephalitis virus, R. rickettsii, B. bacilliformis (Andes mountains), P. falciparum, T. solium Southeast Asia, China, Pacific Rim Japanese encephalitis virus, tickborne encephalitis virus, Nipah virus, P. falciparum, Gnanthostoma species, T. solium Transfusion and transplantation Cytomegalovirus, Epstein-Barr virus, West Nile virus, HIV, tickborne encephalitis virus, rabies virus, iatrogenic CJD, T. pallidum, A. phagocytophilum, R. rickettsii, C. neoformans, Coccidioides species, H. capsulatum, T. gondii Unvaccinated status Varicella zoster virus, Japanese encephalitis virus, poliovirus, measles virus, mumps virus, rubella virus
  10. 10. Possible etiologic agents of encephalitis based on clinical findings Clinical presentation Possible infectious agent General findings Hepatitis Coxiella burnetii Lymphadenopathy HIV, Epstein-Barr virus, cytomegalovirus, measles virus, rubella virus, West Nile virus, Treponema pallidum, Bartonella henselae and other Bartonella species, Mycobacterium tuberculosis, Toxoplasma gondii, Trypanosoma brucei gambiense Parotitis Mumps virus Rash Varicella zoster virus, B virus, human herpesvirus 6, West Nile virus, rubella virus, some enteroviruses, HIV, Rickettsia rickettsii, Mycoplasma pneumoniae, Borrelia burgdorferi, T. pallidum, Ehrlichia chaffeensis, Anaplasma phagocytophilum Retinitis Cytomegalovirus, West Nile virus, B. henselae, T. pallidum
  11. 11. Neurologic findings Cerebellar ataxia Varicella zoster virus (children), Epstein-Barr virus, mumps virus, St. Louis encephalitis virus, Tropheryma whipplei, T. brucei gambiense Cranial nerve abnormalities Herpes simplex virus, Epstein-Barr virus, Listeria monocytogenes, M. tuberculosis, T. pallidum, B. burgdorferi, T. whipplei, Cryptococcus neoformans, Coccidioides species, H. capsulatum Dementia HIV, human transmissible spongiform encephalopathies (sCJD and vCJD), measles virus (SSPE), T. pallidum, T. whipplei Myorhythmia T. whipplei (oculomasticatory) Poliomyelitis-like flaccid paralysis Japanese encephalitis virus, West Nile virus, tickborne encephalitis virus; enteroviruses (enterovirus-71, coxsackieviruses), poliovirus Rhombencephalitis Herpes simplex virus, West Nile virus, enterovirus 71, L. monocytogenes Parkinsonism (bradykinesia, masked facies, cogwheel rigidity, postural instability) Japanese encephalitis virus, St. Louis encephalitis virus, West Nile virus, Nipah virus, T. gondii, T. brucei gambiense
  12. 12. Diagnosis  4. Specific diagnostic studies should be performed for the majority of patients who present with encephalitis (AIII).  5. Additional diagnostic studies should be performed for patients with encephalitis on the basis of specific epidemiologic and clinical clues (A-III).
  13. 13. Diagnostic Studies outside the CNS  6. Cultures of body fluid specimens (e.g., from blood, stool, nasopharynx, or sputum), if clinical and epidemiologic clues are suggestive, should be performed in an attempt to identify various viral, bacterial, and fungal etiologies of encephalitis (B-III); positive results do not necessarily indicate that isolated microorganism is etiology of encephalitis and must be interpreted in the context of the appropriate epidemiologic findings, clinical findings, and other diagnostic study results.  7. Biopsy of specific tissues for culture, antigen detection, nucleic acid amplification tests (such as PCR), and histopathologic examination should be performed in an attempt to establish an etiologic diagnosis of encephalitis (A-III).
  14. 14.  8. Certain causes of encephalitis may be diagnosed by detection of IgM antibodies in serum (A-III)  9. Although acute- and convalescent-phase serum samples are generally not useful in establishing the etiology during the acute presentation in a patient with encephalitis, they may be useful for the retrospective diagnosis of an infectious agent (B-III).  10. Nucleic acid amplification tests (such as PCR) of body fluids outside of the CNS may be helpful in establishing the etiology in some patients with encephalitis (B-III).
  15. 15. Neurodiagnostic Studies  11. MRI is the most sensitive neuroimaging test to evaluate patients with encephalitis (A-I).  12. CT, with and without contrast enhancement, should be used to evaluate patients with encephalitis if MRI is unavailable, impractical, or cannot be performed (B- III).  13. Fluorine-18 fluorodeoxyglucose positron emission tomography (FDG-PET) scanning is not routinely recommended for patients with encephalitis.
  16. 16.  14. Electroencephalography (EEG) is rarely helpful in establishing an etiology in patients with encephalitis, but it has a role in identifying patients with nonconvulsive seizure activity who are confused, obtunded, or comatose and should be performed in all patients with encephalitis (A-III).  15. CSF analysis is essential (unless contraindicated) in all patients with encephalitis (A-III).
  17. 17. Diagnostic Studies in the CNS  16. For certain viral agents, the presence of virus- specific IgM in CSF specimens may be indicative of CNS disease caused by that pathogen (A-III).  17. Nucleic acid amplification tests (such as PCR) should be performed on CSF specimens to identify certain etiologic agents in patients with encephalitis (A-III). Although a positive test result is helpful in diagnosing infection caused by a specific pathogen, a negative result cannot be used as definitive evidence against the diagnosis.
  18. 18.  18. Herpes simplex PCR should be performed on all CSF specimens in patients with encephalitis (A-III). In patients with encephalitis who have a negative herpes simplex PCR result, consideration should be given to repeating the test 3–7 days later in those with a compatible clinical syndrome or temporal lobe localization on neuroimaging (B-III).  19. Viral cultures of CSF specimens are of limited value in patients with encephalitis and are not routinely recommended.  20. Brain biopsy should not be routinely used in patients with encephalitis but should be considered in patients with encephalitis of unknown etiology whose condition deteriorates despite treatment with acyclovir (B-III).
  19. 19. Diagnostic evaluation to consider in determining the microbial etiology in patients with encephalitis Class of microorganism General diagnostic evaluation Viruses -Culture of respiratory secretions and nasopharynx, throat, and stool specimens -CSF PCR for cytomegalovirus, JC virus, human herpesvirus 6, and West Nile virus -DFA of sputum for respiratory viruses -PCR of respiratory specimens -Culture and/or DFA of skin lesions (if present) for herpes simplex virus and varicella zoster virus -Serologic testing for HIV -Serologic testing for Epstein-Barr virus -Serologic testing for St. Louis encephalitis virus, Eastern equine encephalitis virus, Venezuelan equine encephalitis virus, La Crosse virus, West Nile virus -CSF IgM for West Nile virus, St. Louis encephalitis virus, varicella zoster virus -CSF PCR for herpes simplex virus 1, herpes simplex virus 2, varicella zoster virus, Epstein-Barr virus,d enteroviruses
  20. 20. Bacteria -Blood cultures -CSF cultures … -Serologic testing for Mycoplasma pneumoniae -PCR of respiratory secretions for M. pneumoniae Rickettsiae -Serologic testing for Rickettsia rickettsi, Ehrlichia chaffeensis, and Anaplasma phagocytophilum -DFA and PCR of skin biopsy specimen for R. rickettsiae -Blood smears for morulae -PCR of whole blood and CSF specimens for Ehrlichia and Anaplasma species Spirochetes -Serum RPR and FTA-ABS -Serologic testing for Borrelia burgdorferi (ELISA and Western blot), -CSF VDRL -CSF B. burgdorferi serologic testing (ELISA and Western blot); -calculate IgG antibody index -CSF FTA-ABS Mycobacteria -Chest radiograph -PCR and culture of respiratory secretions -CSF AFB smear and culture -CSF PCR (Gen-Probe Amplified Mycobacterium tuberculosis Direct Test)
  21. 21. Fungi -Blood cultures -CSF cultures -Serum and CSF cryptococcal antigen -Urine and CSF Histoplama antigeng -Serum and CSF complement fixing or immunodiffusion antibodies for Coccidioides species Protozoa Serum IgG for Toxoplasma gondii
  22. 22. Treatment Empirical Therapy  21. Acyclovir should be initiated in all patients with suspected encephalitis, pending results of diagnostic studies (AIII).  22. Other empirical antimicrobial agents should be initiated on the basis of specific epidemiologic or clinical factors , including appropriate therapy for presumed bacterial meningitis, if clinically indicated (A-III).  23. In patients with clinical clues suggestive of rickettsial or ehrlichial infection during the appropriate season, doxycycline should be added to empirical treatment regimens (A-III).
  23. 23.  Specific Therapy Viruses  24. Herpes simplex virus: acyclovir is recommended (AI).  25. Varicella-zoster virus: acyclovir is recommended (BIII); ganciclovir can be considered an alternative (C- III); adjunctive corticosteroids can be considered (C-III).  26. Cytomegalovirus: the combination of ganciclovir plus foscarnet is recommended (B-III); cidofovir is not recommended, because its ability to penetrate the blood-brain barrier has been poorly studied.
  24. 24.  27. Epstein-Barr virus: acyclovir is not recommended; use of corticosteroids may be beneficial (C-III), but the potential risks must be weighed against the benefits.  28. Human herpesvirus 6: ganciclovir or foscarnet should be used in immunocompromised patients (B- III); use of these agents in immunocompetent patients can be considered (CIII), but there are not good data on their effectiveness.  29. B virus: valacyclovir is recommended (B-III); alternative agents are ganciclovir (B-III) and acyclovir (C-III).  30. Influenza virus: oseltamivir can be considered (C-III).
  25. 25.  31. Measles virus: ribavirin can be considered (C-III); intrathecal ribavirin can be considered in patients with subacute sclerosing panencephalitis (C-III).  32. Nipah virus: ribavirin can be considered (C-III).  33. West Nile virus: ribavirin is not recommended.  34. Japanese encephalitis virus: IFN-a is not recommended.  35. St. Louis encephalitis virus: IFN-2a can be considered (C-III).  36. HIV: HAART is recommended (A-II).  37. JC virus: reversal of immunosuppression (A-III)—or HAART in HIV-infected patients (A-II)—is recommended.
  26. 26. Bacteria  38. Bartonella bacilliformis: chloramphenicol, ciprofloxacin, doxycycline, ampicillin, or trimethoprim- sulfamethoxazole is recommended (B-III).  39. Bartonella henselae: doxycycline or azithromycin, with or without rifampin, can be considered (C-III).  40. Listeria monocytogenes: ampicillin plus gentamicin is recommended (A-III); trimethoprim-sulfamethoxazole is an alternative in the penicillin-allergic patient (A-III).  41. Mycoplasma pneumoniae: antimicrobial therapy (azithromycin, doxycycline, or a fluoroquinolone) can be considered (C-III).  42. Tropheryma whipplei: ceftriaxone, followed by either trimethoprim-sulfamethoxazole or cefixime, is recommended (B-III).
  27. 27. Mycobacteria  43. Mycobacterium tuberculosis: 4-drug antituberculous therapy should be initiated (A-III); adjunctive dexamethasone should be added in patients with meningitis (B-I). Spirochetes  48. Borrelia burgdorferi: ceftriaxone, cefotaxime, or penicillin G is recommended (B-II)  49. Treponema pallidum: penicillin G is recommended (AII); ceftriaxone is an alternative (B-III).
  28. 28. Rickettsioses and ehrlichioses  44. Anaplasma phagocytophilum: doxycycline is recommended (A-III).  45. Ehrlichia chaffeensis: doxycycline is recommended (AII).  46. Rickettsia rickettsii: doxycycline is recommended (AII); chloramphenicol can be considered an alternative in selected clinical scenarios, such as pregnancy (C-III).  47. Coxiella burnetii: doxycycline plus a fluoroquinolone plus rifampin is recommended (B-III).
  29. 29. Fungi  50. Coccidioides species: fluconazole is recommended (AII); alternatives are itraconazole (B-II), voriconazole (B- III), and amphotericin B (intravenous and intrathecal) (C- III).  51. Cryptococcus neoformans: initial treatment with amphotericin B deoxycholate plus flucytosine (A-I) or a lipid formulation of amphotericin B plus flucytosine (A-II) is recommended.  52. Histoplasma capsulatum: liposomal amphotericin B followed by itraconazole is recommended (B-III).
  30. 30. Protozoa  53. Acanthamoeba: trimethoprim-sulfamethoxazole plus rifampin plus ketoconazole (C-III) or fluconazole plus sulfadiazine plus pyrimethamine (C-III) can be considered.  54. Balamuthia mandrillaris: pentamidine, combined with a macrolide (azithromycin or clarithromycin), fluconazole, sulfadiazine, flucytosine, and a phenothiazine can be considered (C-III).  55. Naegleria fowleri: amphotericin B (intravenous and intrathecal) and rifampin, combined with other agents, can be considered (C-III).
  31. 31.  56. Plasmodium falciparum: quinine, quinidine, or artemether is recommended (A-III); atovaquone-proguanil is an alternative (B-III); exchange transfusion is recommended for patients with 110% parasitemia or cerebral malaria (B-III); corticosteroids are not recommended.  57. Toxoplasma gondii: pyrimethamine plus either sulfadiazine or clindamycin is recommended (A-I); trimethoprimsulfamethoxazole alone (B-I) and pyrimethamine plus either atovaquone, clarithromycin, azithromycin, or dapsone (B-III) are alternatives.  58. Trypanosoma brucei gambiense: eflornithine is recommended (A-II); melarsoprol is an alternative (A-II).  59. Trypanosoma brucei rhodesiense: melarsoprol is recommended (A-II).
  32. 32. Helminths  60. Baylisascaris procyonis: albendazole plus diethycarbamazine can be considered (C-III); adjunctive corticosteroids should also be considered (B-III).  61. Gnathostoma species: albendazole (B-III) or ivermectin (B-III) is recommended.  62. Taenia solium: need for treatment should be individualized; albendazole and corticosteroids are recommended (BIII); praziquantel can be considered as an alternative (C-II).
  33. 33. Postinfectious/postvaccination status  63. Acute disseminated encephalomyelitis: high- dose corticosteroids are recommended (B-III); alternatives include plasma exchange (B-III) and intravenous immunoglobulin (CIII).
  34. 34. GUIDELINES CLINICAL MANAGEMENT OF ACUTE ENCEPHALITIS SYNDROME INCLUDING JAPANESE ENCEPHALITIS GOVERNMENT OF INDIA National Vector Borne Disease Control Programme Directorate General of Health Services, Ministry of Health & Family Welfare AUGUST 2009
  35. 35.  Case definition of Acute Encephalitis Syndrome (AES)-defined as a person of any age, at any time of year with acute onset of fever and a change in mental status (including symptoms such as confusion, disorientation, come, or inability to talk) AND/OR new onset of seizures(excluding simple febrile seizures).
  36. 36. Case classification  a) Laboratory-confirmed JE: A suspected case that has been laboratory-confirmed as JE.  b) Probable JE: A suspected case that occurs in close geographic and temporal relationship to laboratory- confirmed case of JE, in the context of an outbreak.  c) .Acute encephalitis syndrome. (due to agent other than JE): A suspected case in which diagnostic testing is performed and an etiological agent other than JE virus is identified.  d) .Acute encephalitis syndrome. (due to unknown agent ) A suspected case in which no diagnostic testing is performed or in which testing was performed but no etiological agent was identified or in which the test results were indeterminate.
  37. 37. AGENTS OF CLINICALLY IMPORTANT VIRAL ENCEPHALITIS IN INDIA  Japanese encephalitis virus Enteroviruses • Outbreak-2006, east UP (EV 89,76); 2008, Lucknow (EV 71) • Sporadic-2004-06, AMU, UP (EV 71); 2007, Delhi (EV 71)  Herpes simplex virus 1 (HSV-1)  Dengue Virus (encephalopathy)  Measles virus  Chandipura • Outbreak-Andhra Pradesh 2003; Gujarat 2004; Nagpur 2005; Nagpur 2007 • Sporadic-2005-06; Andhra Pradesh  Mumps virus  Chikungunya  Varicella zoster virus (VZV)  Epstein-Barr virus (EBV)  Human immunodeficiency virus (HIV)  Human herpesvirus 6 (HHV-6)  Nipah (Handra) • Outbreak: 2001, Siliguri; 2007, West Bengal  West Nile virus  Kyasanur Forest Disease  Rabies
  38. 38. MRI FINDINGS IN VIRAL ENCEPHALITIS AND SOME MIMICKERS Etiology MRI Finding Herpes simplex encephalitis Abnormal signal intensity in medial temporal lobe, cingulate gyrus, and orbital surface of frontal lobes Japanese B encephalitis Abnormal signal intensity in thalami (87-94%), substantia nigra, and basal ganglia EV 71 Abnormal signal intensity in the dorsal pons, medulla, midbrain, and dentate nuclei of the cerebellum; gigh-signal lesions can also be found in the anterior horn cells of spinal cord in patients with acute flaccid paralysis Chandipura virus Normal Nipah virus Focal subcortical and deep white matter and gray matter lesions; small hyperintense lesions in the white matter, cortex, pons and cerebral peduncles have also been seen.
  39. 39. Varicella Multifocal abnormalities in cortex, associated cerebellitis, vasculitis and vasculopathy Acute disseminated encephalomyelitis Multifocal abnormalities in subcortical white matter; involvement of thalami, basal ganglia, and brainstem also seen West Nile virus Abnormalities in deep gray matter and brainstem (50%); white matter lesions mimicking demyelination may also be seen; meningeal involvement on contrast enhanced images.
  40. 40. GUIDELINES FOR COLLECTION, STORAGE AND TRANSPORT OF SAMPLES Type of sample Guidelines Blood • Collect within 4 days after the onset of illness for isolation of virus and at least 5 days after the onset of illness for detection of IgM antibodies. • A second, convalescent sample should be collected at least 10-14 days after the first sample for serology. • Take clotted blood sample. Separate serum after clot retraction. • Serum should be shipped on wet ice within 48 hours or stored at for a maximum period of 7 days. • In case a delay is anticipated, sera must be frozen at -20°C and should be transported to the specified laboratory on frozen ice packs. • Repeated freezing and thawing can have detrimental effects on the stability of IgM antibodies. Cerebrospinal fluid • Send for cell count, bacteriology, biochemistry and virology - PCR, serology. • May be stored at +4°C if delays in processing for virus culture or viral PCR will be less than 24 hrs. • If greater delays are likely, CSF should be frozen at -80°C.
  41. 41. Swabs (naso-phary-geal, throat, vesicle) • Dacron/ Nylon swabs should be used, and put into virus transport medium. Swabs may be utilized for a range of virus cultures and PCR. Urine 10-20 mL of urine should be collected into sterile containers (without preservatives) for mumps virus culture and mumps PCR; store at -20°C. Stool Stool should be collected for enterovirus culture into clean containers; store at -20°C. Brain biopsy • Brain specimens should be collected unfixed into a sterile container. Brain smears can be used for viral antigen detection by immunofluorescent antibody staining, and for electron microscopy with negative staining. • Emulsified brain tissue is suitable for tissue culture and after proteinase K treatment for PCR.
  42. 42. MICROBIOLOGICAL INVESTIGATIONS AVAILABLE IN ACUTE ENCEPHALITIS SYNDROME Virus Sample/ test Japanese Encephalitis Virus Virus-specific IgM antibody in a single sample of cerebrospinal fluid (CSF) or serum, as detected by an IgM-capture ELISA specifically for JE virus Enteroviral encephalitis -Detection of EV genome by RT-PCR or an equally sensitive and specific nucleic acid amplification test (real time) in CSF -Isolation of virus from serum/stool/throat swab Dengue viral encephalitis Dengue virus-specific IgM antibody in a single sample of CSF as detected by an IgM-capture ELISA HSV Encephalitis -Detection of HSV DNA in CSF by PCR -HSV specific antibody titres in serum and CSF Mumps virus encephalitis Detection of Mumps virus RNA in CSF by PCR Varicella zoster virus encephalitis Detection of VZV DNA by PCR in CSF
  43. 43. Nipah virus -Detection of Nipah virus specific IgM antibodies in serum and CSF by IgM-capture ELISA -PCR from CSF Measles virus Appearance of measles virus specific IgM antibody in the CSF Chandipura virus -PCR from CSF -Detection of specific IgM antibodies in CSF by ELISA
  44. 44. Basic investigations in suspected AES-  Complete blood count (including platelet count), blood glucose, serum electrolytes, liver and kidney function tests, blood culture, arterial blood gas.  Peripheral smear for malarial parasite and rapid diagnostic test for malaria .  Chest X-ray
  45. 45. Lumbar puncture-  CSF should be examined for cytology, biochemistry, gram stain, Ziehl-Nielsen stain for acid fast bacilli, bacterial culture, PCR for HSV 1 and 2, and IgM antibodies for JE and for Dengue virus (if suspected). Concurrent blood sugar must also be measured .  1-2 Ml CSF should be stored for other virological studies, if needed.
  46. 46. PREVENTIVE STRATEGIES-  (i) Surveillance for cases of AES;  (ii) Vector control;  (iii) Reduction in man-vector contact;  (iv) Vaccination.
  47. 47. Immunization-  Although vaccines are under development against many viral agents responsible for AES in children, but primarily it is JE against which vaccines are available for routine use.  Cell culture-derived, live attenuated vaccine: Currently, this is the only JE vaccine available in India.  0.5 mL dose is to be administered subcutaneously to children at eight months of age and a second at two years.
  48. 48. Association of British Neurologists and British Infection Association National Guidelines